NDLI: Expression of a dominant-negative type II transforming growth factor β (TGF-β) receptor in the epidermis of transgenic mice blocks TGF-β-mediated growth inhibition

Content Provider	PubMed Central
Author	Wang, Xiao-jing Greenhalgh, David A. Bickenbach, Jackie R. Jiang, Aibo Bundman, Donnie S. Krieg, Thomas Derynck, Rik Roop, Dennis R.
Copyright Year	1997
Abstract	To determine whether a functional type II receptor of transforming growth factor β (TGF-β) is required to mediate the growth inhibitory effect of TGF-β on the skin in vivo, we have generated transgenic mice that overexpress a dominant negative-type II TGF-β receptor (ΔβRII) in the epidermis. The ΔβRII mice exhibited a thickened and wrinkled skin, and histologically the epidermis was markedly hyperplastic and hyperkeratotic. In vivo labeling with BrdUrd showed a 2.5-fold increase in the labeling index over controls, with labeled nuclei occurring in both basal and suprabasal cells of transgenic epidermis. In heterozygotes, this skin phenotype gradually diminished, and by 10–14 days after birth the transgenic mice were indistinguishable from their normal siblings. However, when F1 mice were mated to homozygosity, perinatal lethality occurred due to the severe hyperkeratotic phenotype, which restricted movement. Cultured primary keratinocytes from ΔβRII mice also exhibited an increased rate of growth in comparison with nontransgenic controls, and were resistant to TGF-β-induced growth inhibition. These data document the role of the type II TGF-β receptor in mediating TGF-β-induced growth inhibition of the epidermis in vivo and in maintenance of epidermal homeostasis.
Starting Page	2386
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	6
Volume Number	94
Language	English
Publisher	The National Academy of Sciences of the USA
Publisher Date	1997-03-18
Access Restriction	Open
Rights Holder	The National Academy of Sciences of the USA
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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